CN116350855A - Reel type nerve conduit with directionally arranged collagen fibers and preparation method and application thereof - Google Patents
Reel type nerve conduit with directionally arranged collagen fibers and preparation method and application thereof Download PDFInfo
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- CN116350855A CN116350855A CN202310399051.5A CN202310399051A CN116350855A CN 116350855 A CN116350855 A CN 116350855A CN 202310399051 A CN202310399051 A CN 202310399051A CN 116350855 A CN116350855 A CN 116350855A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/04—Macromolecular materials
- A61L29/044—Proteins; Polypeptides; Degradation products thereof
- A61L29/045—Collagen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/04—Macromolecular materials
- A61L29/044—Proteins; Polypeptides; Degradation products thereof
- A61L29/048—Other specific proteins or polypeptides not covered by A61L29/045 - A61L29/047
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
- A61L2300/608—Coatings having two or more layers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
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Abstract
The invention discloses a reel type nerve conduit with directionally arranged collagen fibers and a preparation method and application thereof, belonging to the field of medical biological materials. The collagen in the nerve conduit is arranged in an oriented way along the axial direction of the conduit, a friendly bionic environment is provided for nerve cells, and oriented collagen fibers provide guidance clues for nerve cell migration and axon oriented extension; the nerve conduit can be used for bridging defective nerves, guiding nerve cells to grow directionally, and promoting nerve repair reconstruction and functional recovery.
Description
Technical Field
The invention relates to the field of medical biological materials, in particular to a reel type nerve conduit with directionally arranged collagen fibers, and a preparation method and application thereof.
Background
Peripheral nerve injury is a common clinical injury, usually causes motor and sensory dysfunction, has high disability rate for patients, and brings heavy medical and economic burden to society. Damaged peripheral nerves are difficult to reconstruct, and especially, the nerve regeneration ability of a large segment of defects is very limited. The gold standard for repairing large nerve defects is autologous nerve transplantation, however, the donor source is limited, the function of the donated part is seriously lost, and the donor and the receptor are not easily matched. Nerve conduits, also known as artificial nerves and artificial nerve grafts, are tubular structures made of natural and/or synthetic biopolymers that serve as bridges to cover/fill nerve lesions or connect between nerve endings, providing structural support and nutritional support for axon regeneration along the conduit. Nerve conduits have been used to clinically repair nerve damage, overcoming a number of drawbacks of autologous and allogenic nerve transplants, and more professionals believe that nerve conduits can gradually replace nerve transplants, and will play a key role in peripheral nerve repair in the future.
The present nerve conduit is made of natural polymer, synthetic polymer and their compound, and collagen and polycaprolactone are widely used in making nerve conduit. The natural biological polymers such as collagen have excellent biocompatibility and tissue regeneration induction capability, can provide friendly living environment for cells, but have weak mechanical properties, and the synthetic polymers have good mechanical properties but poor biocompatibility and biological activity. Thus, natural biopolymers, which provide a biomimetic environment for cells and synthetic polymers, provide appropriate structural/mechanical support, are commonly used in combination with synthetic polymers.
Nerve conduits come in a variety of structural types, such as hollow bulk single wall, hollow porous single wall, hollow trench single wall, multichannel, single wall internally filled fibers or hydrogels. Nutrient and growth factor penetration are critical requirements for nerve conduits, which are not met by nonporous single wall designs, which have been rarely adopted; the grooves and the multi-channel design can well guide the directional growth of the axons, but the manufacturing technical requirements are high; nerve catheters with hydrogel fillers prevent axonal ingrowth into the catheter, and thus porous single wall and fiber filled structures are most common in nerve catheters currently used clinically, as approved by the FDA
Is a hollow porous single-wall round tube made of I-type collagen protein,>
the 3D nerve conduit is
Based on (a), the inside is filled with a porous matrix composed of type I collagen and chondroitin sulfate-6.
The ideal nerve conduit is required to have a bionic structure, proper mechanical properties, sufficient permeability to provide nutrition, flexibility of use and biodegradability, and can provide proper microenvironment for axon regeneration, improve the nerve regeneration efficiency and quickly restore impaired motor and sensory functions. The nerve conduit used clinically at present is far away from an ideal nerve conduit, is generally used for repairing nerve defects with defect length of less than 3cm, and has unsatisfactory effect on longer nerve repair. In addition, compared with other treatment methods, the autologous nerve transplantation as the gold standard has the best curative effect, but the success rate after the transplantation is only 50%, and the development of the nerve conduit with the excellent curative effect of treating the peripheral nerve injury is always the effort direction of clinicians and scientific researchers.
Disclosure of Invention
The invention provides a reel type nerve conduit with directionally arranged collagen fibers, a preparation method and application thereof, wherein the nerve conduit can be used for bridging defective nerves, guiding nerve cells to directionally grow, and promoting nerve repair reconstruction and functional recovery.
The invention provides a nerve conduit, which is formed by curling a collagen sheet;
the directional ordered arrangement of collagen in the collagen sheet is the natural inherent directional ordered arrangement of collagen in the raw material tissue.
In the nerve conduit, the collagen sheet is curled for at least 1 week to form the nerve conduit;
preferably, the collagen sheet is curled for a plurality of weeks to form a reel, so that the collagen in the nerve conduit is ensured to be arranged in an oriented manner.
The arrangement direction of the collagen in the collagen sheet is the same as or similar to the long axis direction of the nerve conduit.
The nerve conduit is characterized in that the raw material tissue is animal tissue which is rich in collagen and ordered in arrangement and orientation, including but not limited to tendons, ligaments or nerves.
The preparation method of the collagen sheet comprises the following steps:
cutting the raw material tissue into slices, removing cells and macromolecules in the tissue slices, and drying to obtain the collagen slices.
The raw material tissue is animal tissue which is rich in collagen and ordered in arrangement and orientation; including but not limited to at least one of tendons, ligaments, and nerves;
cutting the raw material tissue into slices with a thickness of 5-500 microns, preferably 100-300 microns;
the method for removing the cells in the tissue slice can adopt a repeated freezing and thawing method or adopt a chemical reagent;
specifically, the chemical reagents employed include, but are not limited to, formic acid, peracetic acid, sodium hydroxide, sodium dodecyl sulfate, triton X-100, sodium deoxycholate, and combinations thereof.
The combination treatment includes, but is not limited to, the use of 0.5 to 2% (volume percent) Tris-HCl buffer of Triton X-100 in combination with 1 to 5% (weight percent) sodium deoxycholate solution, the use of 0.1 to 5% (volume percent) peracetic acid/5 to 40% (volume percent) ethanol solution in combination with 0.01 to 0.2M sodium hydroxide/0.05 to 0.2M EDTA solution.
Macromolecules in the removed tissue sections include DNA and RNA, which can be removed with ribonucleases and deoxyribonucleases.
The slicing is to obtain the directional orderly arranged slices of the collagen in the raw material tissue, and the slices are not obtained by thoroughly destroying the tissue structure and then reassembling.
Such means of sectioning include, but are not limited to, frozen sections of tissue or paraffin-embedded sections of tissue.
The invention can modify the collagen sheet firstly and then curl the collagen sheet into a scroll shape to obtain the nerve conduit;
the modification is any one of the following:
(1) Chemically coupling the collagen sheet;
specifically, the chemical coupling reagent is any one or a combination of at least two of aldehyde compounds, carbodiimides, genipin and proanthocyanidins; the aldehyde compound is preferably glutaraldehyde and/or formaldehyde;
(2) Adsorbing or chemically coupling a biological factor or polypeptide promoting nerve regeneration on the collagen sheet;
the biological factor can be at least one of nerve growth factor, brain-derived neurotrophic factor, basic fibroblast growth factor, vascular endothelial growth factor, insulin-like growth factor and platelet-derived growth factor;
the polypeptide can be specifically a polypeptide YIGSR capable of promoting differentiation of nerve cells;
(3) Culturing stem cells directly on the collagen sheet;
specifically, the stem cells are at least one of neural stem cells, bone marrow mesenchymal stem cells, adipose mesenchymal stem cells, umbilical cord mesenchymal stem cells and induced pluripotent stem cells.
After removal of the major non-collagenous components, chemical coupling or biological factor modification of the sheet, the collagen sheet is dried and stored and transported. The drying method comprises the steps of airing, blow-drying or freeze-drying.
The dried collagen sheet may also be subjected to sterilization treatments including ethylene oxide sterilization, high energy electron beam irradiation sterilization or gamma ray sterilization.
The invention further provides application of the nerve conduit in preparation of nerve repair materials or nerve repair.
The preparation method of the nerve conduit comprises the following steps: spreading collagen sheet, moistening with physiological saline, placing a medical silk braided wire parallel to collagen fiber at one end of collagen sheet, crimping collagen sheet, covering silk braided wire, straightening silk braided wire with both hands, rotating to drive collagen sheet to crimp, making into reel with multiple layers of collagen fiber axially arranged, and finally drawing out silk braided wire.
In clinical use, the dry collagen sheet is sheared into a certain shape according to the length and the diameter of the repaired damaged nerve, moistened and curled into the nerve conduit with the required length and diameter.
The nerve missing part has different thickness and length, the nerve conduit has different optimal degradation time in vivo, and the collagen sheet needs to be optimized for degradation time in vivo; optimization of the time of degradation of the collagen sheet in vivo can be achieved by changing the thickness of the collagen sheet, or by chemical coupling.
The invention has the following beneficial effects:
(1) The collagen in the nerve conduit prepared by the invention is derived from allogeneic tissues or xenogeneic tissues, and is characterized in that the collagen in the nerve conduit maintains the natural directional arrangement mode in raw material tissues, and is arranged in an axial direction along the conduit, so that a friendly bionic environment is provided for nerve cells, and directional arranged collagen fibers provide guidance clues for nerve cell migration and directional axon extension;
(2) According to the invention, the collagen sheets which are arranged in a two-dimensional and directional way are curled to form a three-dimensional scroll structure, so that a multilayer filled nerve conduit is realized, collagen in an outer membrane is arranged in order, and the collagen filled in the inner membrane is also arranged in order, thereby being beneficial to the simultaneous directional migration and growth of cells in the inner and outer parts of the nerve and better promoting the regeneration of axons;
(3) The ordered arrangement mode of the nerve conduit collagen is derived from the arrangement mode of the collagen in raw material tissues, the manufacture does not need to directly control collagen molecules and fibers, but only cuts allogenic tissues or xenogenic tissues into slices, carries out treatments such as decellularization and the like, has simple manufacturing process and easily controls the product quality;
(4) The nerve conduit prepared by the invention can cut a dry collagen sheet into a certain shape, moisten and then curl into the nerve conduit with the required length and diameter according to the size of a nerve injury part and the diameter/length of a nerve to be bridged during operation; therefore, the personalized nerve conduit is conveniently rolled out before the nerve is repaired without preparing various types of products during operation.
Drawings
Fig. 1 is a collagen sheet and a surface collagen fiber morphology thereof prepared in example 1.
Fig. 2 is a diagram of bone marrow stem cells grown on collagen sheets.
Fig. 3 is a method of making a nerve conduit.
Fig. 4 is a cross-section of a nerve conduit.
Fig. 5 is a nerve conduit for repairing a rat sciatic nerve defect.
Fig. 6 is a graph of sciatic nerve in rats after 12 weeks of repair.
Detailed Description
The following detailed description of the invention is provided in connection with the accompanying drawings that are presented to illustrate the invention and not to limit the scope thereof.
The experimental methods in the following examples are conventional methods unless otherwise specified.
Materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
Ribonucleases in the examples below were purchased from Sigma-Aldrich under the designation R5503; deoxyribonuclease was purchased from Sigma-Aldrich under the accession number DN25;
ethyl dimethylaminopropyl carbodiimide was purchased from aladine under the trade designation E106172; n-hydroxysuccinimide was purchased from Alatine under the designation H109330;
calcein was purchased from Biyundian under the number C2012.
Example 1 preparation of collagen sheet
Fresh bovine Achilles tendon was purchased from slaughterhouse, a 50mm long segment was cut from the tendinous region thereof, immersed in an OCT frozen section embedding agent, longitudinally sectioned with a frozen microtome to a section thickness of 100 μm, and then tendon sections were immersed in physiological saline to wash out the embedding agent. The tendon slices are repeatedly frozen and thawed for 5 cycles (-80 ℃ for 10 minutes, 37 ℃ for 10 minutes), then treated with ribonuclease (150 IU/mL) and deoxyribonuclease (100 mug/mL) in phosphate buffer solution at 37 ℃ for 4 hours, washed with distilled water, frozen in a refrigerator (-80 ℃ for 10 minutes), and then placed in a freeze pump for freezing and pumping (instrument ultimate vacuum degree is less than or equal to 5 Pa). The photograph of the obtained collagen sheet is shown as A in FIG. 1. Finally, the collagen sheet is sealed in a product packaging bag, gamma irradiation sterilization is carried out at a dose of 25kGy, and the collagen sheet is stored at room temperature. The surface of the collagen sheet was observed with a scanning electron microscope, and collagen fibers were arranged in an oriented and ordered manner (see B in fig. 1).
Collagen sheets derived from bovine sciatic nerve can be prepared by the same method.
Example 2 chemical coupling of collagen sheets
1) The collagen sheet (bovine Achilles tendon) prepared in example 1 was immersed in a coupling buffer (0.1M carbonate, 0.15M NaCl, pH 8.5) containing 1% glutaraldehyde by volume, reacted at room temperature for 6 hours, then rinsed with distilled water, and freeze-dried (frozen at-80℃for 10 minutes in a refrigerator and then freeze-dried in a freeze-pump).
2) The collagen sheet (bovine Achilles tendon) prepared in example 1 was immersed in a coupling buffer (0.1M MES (morpholinoethanesulfonic acid), pH 4.7) containing 50mM ethyl dimethylaminopropyl carbodiimide and 20mM N-hydroxysuccinimide, reacted at room temperature for 2 hours, followed by rinsing with distilled water, freeze-drying (frozen at-80℃for 10 minutes in a refrigerator, and then frozen and dried in a freeze-pump).
3) The collagen sheet (bovine Achilles tendon) prepared in example 1 was immersed in physiological saline containing 1% genipin (mass percent), reacted at room temperature for 24 hours, then rinsed with distilled water, freeze-dried (frozen at-80 ℃ C. In a refrigerator for 10 minutes, and then freeze-dried in a freeze pump).
Example 3 biological factor modified collagen sheet
After chemically coupling collagen sheets with glutaraldehyde or ethyldimethylaminopropyl carbodiimide by the method 1) or 2) of example 2, the collagen sheets were rinsed with distilled water, cooled to half-dry at room temperature, and uniformly (50. Mu.L/cm) on the collagen sheets 2 ) Dripping nerve growth factor (mouse nerve growth factor, nerve growth factor extracted from submandibular gland of mouse, which is a bioactive protein with molecular weight of 26.5 KD) water solution (50 μg/mL), standing at 4deg.C for 12 hr, lyophilizing (freezing at-80deg.C for 10 min, and then freezing and draining in a freeze pump).
EXAMPLE 4 collagen sheet loaded with Stem cells
The collagen sheet (bovine Achilles tendon) prepared in example 1 was trimmed to a size of 1.0 cm. Times.1.5 cm, placed on the bottom of a bacterial culture dish, infiltrated with cell culture medium (DMEM supplemented with 10% (v/v) fetal bovine serum), and 200. Mu.l of rat bone marrow stem cell suspension (2X 10) 5 cell/mL) was uniformly loaded onto collagen sheets, and then the material was placed into a cell culture tank at 37℃with 5% (v/v) CO 2 Culturing for 3 hours, slowly adding culture medium along the wall of the culture dish after the cells are fully adhered to the material, completely immersing the collagen sheet, and replacing the culture medium every other day. After 7 days of culture, the samples were stained with calcein, and cell morphology was examined under a laser confocal scanning microscope to observe cell alignment, and it was found that many cell long axis directions were aligned along the collagen fiber direction (fig. 2, white arrows represent the collagen fiber direction).
Example 5 preparation of nerve conduit
Taking out rectangular collagen sheet (10) from the packaging bag, spreading collagen fiber arrangement direction expressed by virtual and real line trend (figure 3), wetting with physiological saline, placing a medical silk braided wire (11) parallel to the collagen fiber at one end of the collagen sheet, curling the collagen sheet to just cover the silk braided wire, straightening the silk braided wire with both hands, rotating to drive the collagen sheet to curl, making a reel (12) axially arranged by multiple layers of collagen fibers, and finally extracting the silk braided wire from the nerve conduit. The collagen sheet can be cut into different shapes according to the needs to be curled, for example, the collagen sheet is cut into a shape with a wide upper part and a narrow lower part, the collagen sheet is curled according to the same method as the above, and the reel type nerve conduit with the sleeves at the two ends is manufactured. If a thick nerve conduit is needed, after one collagen sheet is rolled up, the rolled up scroll is used as the axis, and the 2 nd and 3 rd … … collagen sheets are continuously rolled up until the required diameter is reached, so that the nerve is repaired. Nerve catheters were embedded with OCT frozen section embedding medium, frozen, sectioned transversely, stained with aniline blue, photographed, and the results are shown in fig. 4.
Example 6 repair of rat sciatic nerve
12 SD rats with a weight of about 300-350 g are selected, randomly distributed to a damage group, an autograft group, a nerve conduit group and a nerve conduit group modified by nerve growth factors, 2% (weight percent) sodium pentobarbital is injected into the abdominal cavity of the rats for anesthesia, the rats are fixed on an operating table after anesthesia, the left thigh is shaved on the outer side Mao Beipi, iodine is disinfected, skin is cut for 1cm at the back median depression, muscles are carefully separated along the muscle gap, sciatic nerves (20) are exposed (figure 5), and the middle sciatic nerves are resected to form 10mm defects. The injury group is not repaired after the 10mm nerve defect is manufactured; cutting off the sciatic nerve by 10mm in the autograft group, and performing in-situ suturing; the nerve conduit group was prepared by using the collagen sheet (bovine Achilles tendon) prepared in example 1, and a nerve conduit with a diameter slightly thicker than that of sciatic nerve and a length of 10mm was prepared according to the method of example 5, the distal end and the proximal end of the damaged nerve were connected, and the joint was sutured with 9-0 surgical suture (fig. 5); nerve growth factor modified nerve conduit group was prepared by using the nerve growth factor modified collagen sheet (ethyl dimethylaminopropyl carbodiimide coupling) prepared in example 3, and a nerve conduit with a diameter slightly thicker than that of sciatic nerve and a length of 10mm was prepared according to the method of example 5, the distal and proximal ends of the damaged nerve were connected, and the joint was sutured with 9-0 surgical suture. After nerve suturing is completed, the incision is closed by suturing layer by layer, and the muscles and epidermis are sutured with 4-0 surgical sutures. All rats were housed under standard experimental conditions and were euthanized 12 weeks after surgery, and the sciatic nerve of the nerve conduit group was found to have been morphologically connected (fig. 6), with the middle thinner portion being the regenerated nerve. The tibialis anterior muscle is taken from the experimental side and the non-operative control side of each rat, the weight of the muscle is measured, the weight ratio of the operative side to the non-operative tibialis anterior muscle on the opposite side is 0.171, 0.429, 0.335 and 0.412 in the injury group, the autograft group, the nerve conduit group and the nerve conduit group modified by nerve growth factor, and the study result proves that the nerve conduit can repair the rat sciatic nerve defect, remarkably slows down the atrophy of the tibialis anterior muscle, and the nerve growth factor modification is helpful for repairing the rat sciatic nerve defect by the nerve conduit.
Claims (9)
1. A nerve conduit, characterized by: the nerve conduit is formed by curling a collagen sheet;
the directional ordered arrangement of the collagen in the collagen sheet is natural inherent directional ordered arrangement of the collagen in the raw material tissue.
2. A nerve conduit according to claim 1, wherein: the collagen sheet is curled for at least 1 week to form a nerve conduit;
preferably, the collagen sheet is rolled for a plurality of weeks to form a roll.
3. The nerve conduit according to claim 1 or 2, wherein: the arrangement direction of the collagen in the collagen sheet is the same as or similar to the long axis direction of the nerve conduit.
4. A nerve conduit according to any one of claims 1-3, wherein: the preparation method of the collagen sheet comprises the following steps:
cutting the raw material tissue into slices, removing cells and macromolecules in the tissue slices, and drying to obtain the collagen slices.
5. A nerve conduit according to claim 4, wherein: the raw material tissue is animal tissue which is rich in collagen and ordered in arrangement and orientation; in particular at least one of tendons, ligaments and nerves;
the thickness of the flakes is 5 to 500 microns, preferably 100 to 300 microns;
the method for removing the cells in the tissue slice adopts a repeated freezing and thawing method or adopts a chemical reagent;
the macromolecules include DNA and RNA that are removed with ribonucleases and deoxyribonucleases.
6. The nerve conduit according to any one of claims 1-5, wherein: chemically coupling the collagen sheet;
specifically, the chemical coupling reagent is any one or a combination of at least two of aldehyde compounds, carbodiimides, genipin and proanthocyanidins.
7. The nerve conduit according to any one of claims 1-5, wherein: adsorbing or chemically coupling a biological factor or polypeptide promoting nerve regeneration on the collagen sheet;
the biological factor can be at least one of nerve growth factor, brain-derived neurotrophic factor, basic fibroblast growth factor, vascular endothelial growth factor, insulin-like growth factor and platelet-derived growth factor;
the polypeptide may specifically be a polypeptide YIGSR capable of promoting differentiation of nerve cells.
8. The nerve conduit according to any one of claims 1-5, wherein: culturing stem cells directly on the collagen sheet;
specifically, the stem cells are at least one of neural stem cells, bone marrow mesenchymal stem cells, adipose mesenchymal stem cells, umbilical cord mesenchymal stem cells and induced pluripotent stem cells.
9. Use of the nerve conduit of any one of claims 1-8 in the preparation of a nerve repair material or nerve repair.
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| CN2022112127239 | 2022-09-30 |
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| CN202310399051.5A Pending CN116350855A (en) | 2022-09-30 | 2023-04-14 | Reel type nerve conduit with directionally arranged collagen fibers and preparation method and application thereof |
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